Cell micromanipulation with HAIRS substrates

Amy Sutton

 

Figure 1: Mechanically active cell culture surfaces [4].


Mechanical forces present in the cell’s environment have a significant impact on cell gene expression and behavior, and play an important regulatory role in tissue development and function [1]. Dysregulation of these processes is an important contributor to tumor metastasis [2]. Studying how forces are translated into different biological outcomes is thus an active area of research that has many far-ranging implications. However, progress on the complex topics of mechanical signaling in cell networks has been hampered by the limitations of the available tools to apply precise forces on cells in controlled in vitro experiments [3]. As part of my Ph.D. work, I have previously developed a new advanced material that offers a powerful new method to mechanically perturb cells [4]. Most significantly, the technique allows us to mechanically strain single cells among a confluent monolayer in vitro via deformations of the underlying growth plane that laterally displace a subset of the cell’s attachment points (focal adhesions) to the ECM-coated surface by several microns (Fig. 1). This will improve and expand our capabilities to study mechanotransduction in cell networks experimentally compared to what was previously possible [5,6]. Although this methodology is broadly applicable and I will use it to explore diverse mechanobiology questions, my core project will revolve around analyzing force propagation between adherent cells (comparison between healthy and malignant cell types). The hypothesis of our proposed project is that the distance and amplitude of propagated strain across cells depends on the pre-stress state of the cells, and their mechanical anisotropy. This work will reveal how mechanical signals are transmitted intercellularly, leading to mechanosensor protein activation in distant cells.



1.    Heisenberg, CP; Bellaïche, Y. “Forces in tissue morphogenesis and patterning”, Cell, 153:948-962, 2013. 

2.    Kumar, S; Weaver, VM. “Mechanics, malignancy, and metastasis: the force journey of a tumor cell”, Cancer 

       Metastasis Rev, 28:113-127, 2009. 

3.    Kim, DH et al. “Microengineered platforms for cell mechanobiology”, Annu Rev Biomed Eng, 11:203-233, 

       2009. 

4.    Sutton, A et al. “Photothermally triggered actuation of hybrid materials as a new platform for in vitro cell 

       manipulation”, Nat Commun, 8, 14700 doi: 10.1038, 2017. 

5.    Bambardekar, K et al. “Direct laser manipulation reveals the mechanics of cell contacts in vivo”, PNAS, 

       112:1416-1421, 2015. 

6.    Kassianidou, E et al. “Geometry and network connectivity govern the mechanics of stress fibers”, PNAS, 

       114:2622-2627, 2017.

McGill University is located on land which has long served as a site of meeting and exchange amongst Indigenous peoples. We honor, recognize, and respect these nations as the traditional stewards of the lands and waters on which we meet today. 

Dr. Allen Ehrlicher

Department of Bioengineering

McConnell Engineering Building

3480 University Street, Room 350

Montreal, Quebec H3A 2A7

Phone: 514-714-8239

Fax: 514-398-7379

Email: allen.ehrlicher@mcgill.ca

Office: McConnell Engineering Building 358